Association of the CYP2B6 gene with anti-tuberculosis drug-induced hepatotoxicity in a Brazilian Amazon population
Highlights • Thirty-one patients out of 220 subjects developed drug-induced hepatotoxicity. • The results for the CYP3A5 gene were not significant among the investigated groups. • The results for the CYP2B6 gene were significant among the investigated groups.
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| Published in: | International journal of infectious diseases Vol. 33; no. C; pp. 28 - 31 |
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| Abstract | Highlights • Thirty-one patients out of 220 subjects developed drug-induced hepatotoxicity. • The results for the CYP3A5 gene were not significant among the investigated groups. • The results for the CYP2B6 gene were significant among the investigated groups. |
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| AbstractList | Objectives: The treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to examine the effect of two gene polymorphisms, one in the CYP2B6 (rs3745274) gene and one in the CYP3A5 (rs776746) gene, on the development of hepatotoxicity in patients treated with anti-TB drugs in a Brazilian Amazon population. Methods: TB patients who were treated with anti-TB drugs were examined for hepatotoxicity, an adverse effect that is characterized by liver damage. The genotype frequencies of the CYP2B6 and CYP3A5 genes examined in this study were assessed using RT-PCR. Results: Thirty-one of the 220 subjects (14.1%) included in this study developed drug-induced hepatotoxicity. The result was significant when the TT homozygous mutant of the CYP2B6 gene was analyzed with additional key variables (p = 0.046; odds ratio (OR) 0.063, 95% confidence interval (CI) 0.004–0.955), which may explain the hepatotoxicity results in this study. Using a univariate statistical model to associate the CYP3A5 gene A6986G polymorphism with the examined drugs, the results did not differ between samples from individuals with and without hepatotoxicity (p = 0.176; OR 0.562, 95% CI 0.255–1.238). Conclusions: The G516T polymorphism in the CYP2B6 gene is a key predictor of the therapeutic response to treatment in TB patients. •Thirty-one patients out of 220 subjects developed drug-induced hepatotoxicity.•The results for the CYP3A5 gene were not significant among the investigated groups.•The results for the CYP2B6 gene were significant among the investigated groups. The treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to examine the effect of two gene polymorphisms, one in the CYP2B6 (rs3745274) gene and one in the CYP3A5 (rs776746) gene, on the development of hepatotoxicity in patients treated with anti-TB drugs in a Brazilian Amazon population. TB patients who were treated with anti-TB drugs were examined for hepatotoxicity, an adverse effect that is characterized by liver damage. The genotype frequencies of the CYP2B6 and CYP3A5 genes examined in this study were assessed using RT-PCR. Thirty-one of the 220 subjects (14.1%) included in this study developed drug-induced hepatotoxicity. The result was significant when the TT homozygous mutant of the CYP2B6 gene was analyzed with additional key variables (p=0.046; odds ratio (OR) 0.063, 95% confidence interval (CI) 0.004–0.955), which may explain the hepatotoxicity results in this study. Using a univariate statistical model to associate the CYP3A5 gene A6986G polymorphism with the examined drugs, the results did not differ between samples from individuals with and without hepatotoxicity (p=0.176; OR 0.562, 95% CI 0.255–1.238). The G516T polymorphism in the CYP2B6 gene is a key predictor of the therapeutic response to treatment in TB patients. The treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to examine the effect of two gene polymorphisms, one in the CYP2B6 (rs3745274) gene and one in the CYP3A5 (rs776746) gene, on the development of hepatotoxicity in patients treated with anti-TB drugs in a Brazilian Amazon population. TB patients who were treated with anti-TB drugs were examined for hepatotoxicity, an adverse effect that is characterized by liver damage. The genotype frequencies of the CYP2B6 and CYP3A5 genes examined in this study were assessed using RT-PCR. Thirty-one of the 220 subjects (14.1%) included in this study developed drug-induced hepatotoxicity. The result was significant when the TT homozygous mutant of the CYP2B6 gene was analyzed with additional key variables (p=0.046; odds ratio (OR) 0.063, 95% confidence interval (CI) 0.004-0.955), which may explain the hepatotoxicity results in this study. Using a univariate statistical model to associate the CYP3A5 gene A6986G polymorphism with the examined drugs, the results did not differ between samples from individuals with and without hepatotoxicity (p=0.176; OR 0.562, 95% CI 0.255-1.238). The G516T polymorphism in the CYP2B6 gene is a key predictor of the therapeutic response to treatment in TB patients. OBJECTIVESThe treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to examine the effect of two gene polymorphisms, one in the CYP2B6 (rs3745274) gene and one in the CYP3A5 (rs776746) gene, on the development of hepatotoxicity in patients treated with anti-TB drugs in a Brazilian Amazon population.METHODSTB patients who were treated with anti-TB drugs were examined for hepatotoxicity, an adverse effect that is characterized by liver damage. The genotype frequencies of the CYP2B6 and CYP3A5 genes examined in this study were assessed using RT-PCR.RESULTSThirty-one of the 220 subjects (14.1%) included in this study developed drug-induced hepatotoxicity. The result was significant when the TT homozygous mutant of the CYP2B6 gene was analyzed with additional key variables (p=0.046; odds ratio (OR) 0.063, 95% confidence interval (CI) 0.004-0.955), which may explain the hepatotoxicity results in this study. Using a univariate statistical model to associate the CYP3A5 gene A6986G polymorphism with the examined drugs, the results did not differ between samples from individuals with and without hepatotoxicity (p=0.176; OR 0.562, 95% CI 0.255-1.238).CONCLUSIONSThe G516T polymorphism in the CYP2B6 gene is a key predictor of the therapeutic response to treatment in TB patients. Highlights • Thirty-one patients out of 220 subjects developed drug-induced hepatotoxicity. • The results for the CYP3A5 gene were not significant among the investigated groups. • The results for the CYP2B6 gene were significant among the investigated groups. |
| Author | Silva, Cleonardo Augusto Braga, Ana Cristina Oliveira Fernandes, Débora Christina Ricardo Oliveira Ribeiro-dos-Santos, Andrea Santos, Sidney Santos, Ney Pereira Carneiro Moraes, Milene Raiol |
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| CitedBy_id | crossref_primary_10_1016_j_meegid_2017_04_001 crossref_primary_10_4292_wjgpt_v12_i3_40 crossref_primary_10_1186_s13643_018_0861_z crossref_primary_10_1002_jat_3175 crossref_primary_10_1111_jcpt_13132 crossref_primary_10_3390_ijerph17010210 crossref_primary_10_1016_j_ijid_2019_02_025 crossref_primary_10_1016_j_ijid_2016_12_002 crossref_primary_10_1016_j_taap_2023_116770 |
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| Keywords | Tuberculosis CYP2B6 Hepatotoxicity CYP3A5 |
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| Snippet | Highlights • Thirty-one patients out of 220 subjects developed drug-induced hepatotoxicity. • The results for the CYP3A5 gene were not significant among the... •Thirty-one patients out of 220 subjects developed drug-induced hepatotoxicity.•The results for the CYP3A5 gene were not significant among the investigated... The treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to examine the... OBJECTIVESThe treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to... Objectives: The treatment of tuberculosis (TB) remains a challenge owing to the high incidence of drug-induced hepatotoxicity. The aim of this study was to... |
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| SubjectTerms | Adult Aged Antitubercular Agents - adverse effects Antitubercular Agents - therapeutic use Brazil CYP2B6 CYP3A5 Cytochrome P-450 CYP2B6 - genetics Cytochrome P-450 CYP3A - genetics Female Genotype Hepatotoxicity Humans Infectious Disease Liver - drug effects Male Middle Aged Polymorphism, Single Nucleotide Pulmonary/Respiratory Tuberculosis Tuberculosis - drug therapy Tuberculosis - genetics |
| Title | Association of the CYP2B6 gene with anti-tuberculosis drug-induced hepatotoxicity in a Brazilian Amazon population |
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